塞瑞替尼450 mg随餐服用治疗中国ALK阳性非小细胞肺癌患者的安全性及近期疗效分析

背景与目的间变性淋巴瘤激酶(anaplastic lymphoma kinase,ALK)染色体易位为非小细胞肺癌(nonsmall cell lung cancer,NSCLC)常见的驱动基因。塞瑞替尼为第二代的ALK抑制剂,可为ALK阳性转移性NSCLC患者带来生存获益,但国内尚无塞瑞替尼用药安全性及疗效的研究报道。因此本研究拟通过真实世界研究来探讨塞瑞替尼450 mg随餐服用治疗中国ALK阳性NSCLC患者的安全性及近期疗效。方法回顾性分析2018年10月-2019年12月期间就诊于四川省8家医疗机构口服塞瑞替尼450 mg/d随餐治疗的ALK阳性NSCLC患者,收集患者基本信息、治疗期间不良事件(adverse effects,AEs)及疗效数据等资料,评价其安全性及初步疗效。结果研究共纳入109例患者,随访至2020年1月23日,中位服药时间为5.87个月(范围:0.4个月-15.7个月),总体不良事件发生率为89.9%,3级-4级不良事件发生率为22.9%。最常见AEs(主要为1级-2级)为腹泻(60.6%)、丙氨酸氨基转移酶(alanine aminotransferase,ALT)升高(38.5%)及门冬氨酸氨基转移酶(aspartate aminotransferase,AST)升高(37.6%)。至随访截止,共45例患者停药,总体客观缓解率(objective response rate,ORR)为37.6%(95%CI:28.5%-47.4%),疾病控制率(disease control rate,DCR)为86.2%(95%CI:78.3%-92.1%)。结论真实世界中,塞瑞替尼450 mg随餐服用的给药方式在中国ALK阳性NSCLC患者中具有良好的安全性及疾病控制率,但需要更大样本量的前瞻性研究来进一步验证。

Effect of pretreatment with different concertrations of morphine, fentanyl and tramadol on the differentiation of human helper T cells in vitro

Objective： To investigate and compare the .effects of different concentrations of morphine, fentanyl and tramadol on the differentiation of human adult helper T cells in vitro. Methods： Twenty out-patients without immune disease were selected and their peripheral blood was collected. Then the Whole blood of peripheral blood mononuclear cells （PBMCs） were pretreated with different concentration of morphine, fentanyl and tramadol for 24 h. The level of CD4^＋ IFN-γ^＋ IL-2^＋/CD4^＋ IL-4^＋ IL-10^＋ was analyzed by three-color flow cytometry, and the CD4^＋ CCR5^＋ and CD4^＋ CCR3 ^＋ cells were counted to observe the imbalance of Th2/Th2. Results： The number of Th2 increased significantly and the ratio of Th2/Th2 decreased dramatically compared with the control group, and there was a dose-dependent fashion in all drugs. Conclusion： Morphine, fentanyl and tramadol can direct Th0 cells toward Th2 differentiation, especially morphine and fentanyl.

Intrathecal co-administration of ketamine and morphine preventing activation of astrocytes and decreasing releases of IL-1β and IL-6 from spinal cord in rats of morphine tolerance

Objective： To investigate the effects of intrathecal administration of ketamine, a non-competitive N-methy-D-aspartate receptor antagonist, combined with morphine on the activation of astrocytes and releases of IL-1β and IL-6 from spinal cord in the rats of morphine tolerance. Methods： Twenty-seven Sprague-Dawley male rats were randomly divided into sham-operated, morphine tolerance, and morphine plus ketamine group. The subarachnoid catheterication of all the rats was prepared by the method of Jianping Yang. Morphine 20μg in 10μl was adminstrated intrathecally to induce spinal morphine tolerance once daily for 5 consecutive days. Morphine and ketamine 250μg in 10μl total volume was given in morphine plus ketamine group. Three groups all received intrathecal morphine 5μg in 10μl for morphine challenge test at 24h after last administration of the morphine. After morphine challenge test, lumbar spinal tissues were taken for measurement of glial fibrillary acidic protein （GFAP） of astrocyte in lumbar spinal horn cord by immunohistochemistry and IL-1β and IL-6 of spinal cord by ELISA. Results： The decrease of %MPE induced by chronic intrathecal morphine was inhibibed by ketamine and hyperalgesia and allodynia induced by morphine-withdrawl were alleviated. The average areas, the average absorbency （A^-）, the integral absorbency （A） of GFAP immuno-reactive cells in the dorsal horn, and IL-1β and IL-6 of spinal cord were significantly larger in morphine tolerance group than in morphine plus ketamine group. Conclusion：Co-administration of ketamine and morphine enhance antinociceptive effect of morphine and prevent the development of morphine tolerance. Ketamine might attenuate the activation of astrocytes and inhibit the release of IL-1β and IL-6 from spinal cord in repeated intrathecal morphine rats.

Comparative cost analysis of three different anesthesia methods in gynecological laparoscopic surgery

In the current study,we assessed and evaluated the costs and benefits of three popular methods of general anesthesia practiced in our department for gynecological laparoscopic surgery in recent years.Sixty adult female patients who underwent elective gynecological laparoscopic surgery under general anesthesia were randomly divided into three groups:group Ⅴ,group Ⅰ and group C.In group Ⅴ,anesthesia was induced intravenously with midazolam,remifentanil,propofol and vecuronium,and maintained with continuous infusion of propofol and remifentanil.In group Ⅰ,anesthesia was intravenously induced with midazolam,fentanyl,propofol and vecuronium,and maintained with inhaled isoflurane and intravenous bonus of fentanyl.In group C,anesthesia was induced as in group Ⅰ,but maintained with isoflurane inhalation combined with propofolremifentanil infusion.All patients received vecuronium for muscle relaxation.Perioperative incidences of complications and total anesthesia costs for patients in all groups were recorded.In addition,postoperative satisfaction of the patients was also noted,and similar outcomes of the satisfaction were reported in all 60 patients.Although there was no statistical significance among groups,the incidence of postoperative nausea and vomiting were higher in group C,and the rates of shivering and the needs for analgesics were higher in group Ⅴ.Anesthesia costs in group Ⅰ were the lowest.Therefore,it is concluded that the costs of anesthesia induced with midazolam,fentanyl,propofol,vecuronium,and maintained with isoflurane,fentanyl and vecuronium are cheapest,and there is no significant difference in patients’satisfaction and safety among the three above-mentioned methods of anesthesia in our department.

Construction of an immortalized neural progenitor cell strain and analysis of its immunogenicity

Neural progenitor cells(NPC)are those that are the source of neural cells for cell transplantation and gene therapy.The shortage in quantity and the limited life spans of primary cultured cells limit its widespread use in basic research.Immortalized NPC,which also possess the capacity of self-renewal and can proliferate infinitely,can produce a large number of NPCs with stable phenotype and genotype.Here we report that an immortalized neural progenitor cell strain,which we named as INPC,was suc-cessfully established by gene-transfer of simian virus 40 large T antigen gene mediated by liposomes.The INPC retained the biological characteristics of its original cells and provided a safe and reliable cell platform for the treat-ment of central nervous system diseases and transgenic cell transplantation.INPC could express low levels of MHC antigens which was down-regulated after differentiation.This indicates that INPC possesses poor immunogenicity.The immortalized cells may show good long-term survival and do not elicit an acute immunological response follow-ing transplantation.